The proliferation of estrogen (E)-sensitive rat pituitary and human breast tumor cells in an "in animal-in culture" system is the central issue studied in this lab. The effect of estradiol-17 beta (E2) on specific protein synthesis and its relation with the proliferation of these E2 target cells will be characterized. These cells carry estrophilins and multiply faster in animals to which E2 is administered than in those in which E2 is lacking. The pituitary tumor cells are prevented from proliferating in rats during the perinatal period and in alpha-fetoprotein (AFP)-secreting hepatoma-bearing isogenic rats. AFP is likely to be the cell multiplication inhibitor in these circumstances according to experiments carried out with animals and in culture. Other estrophilin-carrying cells that behave autonomously when injected into rats supplemented with E2 do not recognize the inhibitory properties of AFP. Further characterization of the interaction of AFP and E2-sensitive cells will be done. On the basis of evidence that indicatesthat E2 affects cell multiplication of its target cells in an indirect and negative fashion, data are being gathered from experiments with rat and human (MCF7) cells. So far results are compatible with the proposition for a significant role played by circulating and intracellular (shut-off mechanism) inhibitors of cell proliferation. Efforts to characterize and purify these inhibitors are currently under way. (D)